tbuckley/cabot-search huggingface dataset:
P55 Real-world clinical and patient-reported outcomes of talimogene laherparepvec (T-VEC) treatment for melanoma in transit and nodal metastases at a UK centre
Authors: Hannah Bennett, Kellie Butterfield, Joanne Robinson, Joh Sugden, Andrew Muinonen-Martin, Angana Mitra
Journal: British Journal of Dermatology (2023)

Abstract Talimogene laherparepvec (T-VEC) is a National Institute for Health and Care Excellence-approved oncolytic viral intralesional immunotherapy licensed for unresectable stage III(B)–IV(M1a) melanoma. It is a genetically modified herpes simplex virus that selectively replicates in tumour cells, leading to local and systemic antitumour immune responses, improving overall survival. The randomized phase III OPTiM trial reported a complete response in 28.2% of patients (Andtbacka RH, Collichio F, Harrington KJ et al. Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec vs. granulocyte-macrophage colony-stimulating factor in unresectable stage III–IV melanoma. J Immunother Cancer 2019; 7:145). We report a retrospective review of clinical and patient-reported outcomes of a dermatology-led T-VEC service at a regional UK melanoma centre between January 2019 and January 2023. Treatment involves a loading dose and then two-weekly nurse-delivered intralesional injections. Patient demographics, clinical characteristics, toxicities, treatment responses and patient satisfaction were recorded. Sixteen patients (11 women and five men) were treated; the average patient age was 73 years (range 42–87). Seven patients had stage IIIB disease, six stage IIIC and three stage IVM1a. Eight had received prior nonsurgical treatments (adjuvant therapy, electrochemotherapy, diphencyprone). The number of lesions treated per visit ranged from 1 to 24 (median 5) over a median of six visits (range 2–24). Four patients (25%) had a complete response (CR), with median time to CR being 8 weeks; all have maintained the response (range 6–45 months). Eight (50%) showed partial response (PR), with three continuing treatment. Nine patients overall had progressive disease (five in the PR group and four who were nonresponders). In total, five patients died. Patients experienced mainly flu-like symptoms (44%), pyrexia (31%), fatigue (19%), muscle pain (19%), nausea (19%), headache (19%), diarrhoea (6%), joint pain (6%), local swelling (19%), lymphadenopathy (6%) and mild pain (25%). No grade 3 or 4 toxicity occurred. A patient satisfaction questionnaire was returned by seven of eight patients who completed treatment. All said they received adequate information to make treatment decisions. Eighty-six per cent rated the service excellent. Our results show comparable efficacy and side-effects to published clinical trials and demonstrate that T-VEC is a well-tolerated and safe treatment option, delaying or potentially avoiding need for more toxic systemic agents. We highlight that dermatologists and nurse specialists are well placed to deliver T-VEC in patients with melanoma.
H13 Leprosy and psoriasis: a heated controversy
Authors: Rabia Sarfraz, Eman Butt
Journal: British Journal of Dermatology (2023)

Abstract In the Old Testament, the term ‘Lepra’ was used to describe many skin diseases, including psoriasis, eczema, vitiligo, alopecia areata and boils. The word ‘leprosy’ was derived from this and was previously used as a generic term that included multiple inflammatory dermatological diseases. It was a disorder of great religious significance during ancient times, with intense stigmatization—‘lepers’ were pronounced unclean by priests. Hippocrates (460–377 Bc), the Greek ‘father of medicine’, can be credited with being the first to separate medicine from religious superstition. However, there was little differentiation between leprosy and psoriasis, two distinct diseases we know today. He used the word ‘psora’ to describe itch, and ‘lopoi’ to describe the dry and scaly features of skin conditions, thus continuing the confusion between leprosy and psoriasis. The failure to differentiate psoriasis as its own clinical entity from leprosy meant that for many centuries, patients with psoriasis also suffered the same cruel fate as those with leprosy in society. Those suffering from leprosy were wrongly believed to be highly contagious and were forced to carry a bell or clapper to announce their approach to those who were considered healthy. They were required to wear distinctive clothing so that they were easy to recognize by the public, and were not permitted to talk to or even touch a healthy person. They were outcast in society and could only mix with other ‘lepers’. In 1313, Philip the Fair of France horrifically ordered all those outcasts to be burned at the stake. In 1809, Robert Willan (1757–1812), an English doctor, marvellously developed a simple classification of skin diseases that offered a clear description of the different types of psoriasis. This was a crucial milestone in the recognition of psoriasis as a separate skin disease from leprosy. However, while he was the first person to describe psoriasis as a separate condition, he failed to eliminate leprosy completely as an associated disease. He used the term ‘lepra vulgaris’ to discuss modern psoriasis, which once again further perpetuated the confusion between psoriasis and leprosy. Ultimately, it was Ferdinand von Hebra (1816–1880), an Austrian physician, who permanently shed the term ‘lepra’ from the description of psoriasis in the 1800s, finally allowing the two diseases to be separate.
PA05 A rare case of cardiocutaneous syndrome in a young child
Authors: Susanna Marini, Ru Katugampola
Journal: British Journal of Dermatology (2023)

Abstract A 19-month-old infant came to our attention showing clinical signs consistent with focal keratoderma limited to the palms and soles, dystrophic pachyonychia of all his nails and scalp alopecia characterized by sparse curly hair. His oral cavity examination revealed periodontitis, early tooth decay and notching of the incisor teeth. The patient is the second child of a nonconsanguineous, otherwise healthy couple. No other family members were reported to have similar skin and oral alterations. Based on the characteristic appearance of his cutaneous lesions, he was investigated for a palmoplantar keratoderma disorder and was subjected to genetic testing. Results confirmed a mutation within DSP, a gene responsible for encoding the most abundant component of desmosomes, a major cell adhesion junction, particularly prominent in epidermal and cardiac tissue. Mutations in genes encoding desmosomal components are known to be associated with a broad spectrum of phenotypical alterations of skin and hair structures. The same genetic anomaly accounts for 40–50% of cases of arrhythmogenic cardiomyopathy (Pigors M, Schwieger-Briel A, Cosgarea R et al. Desmoplakin mutations with palmoplantar keratoderma, woolly hair and cardiomyopathy. Acta Derm Venereol 2015; 95:337–40). Despite being asymptomatic, our young patient was referred to cardiology for further investigations and surveillance. At the age of 7 years, routine electrocardiography revealed new conduction abnormalities. An echocardiogram confirmed a dilated cardiomyopathy that, combined with the previously described cutaneous and oral alterations, led to a diagnosis of cardiocutaneous syndrome. An overview of the clinical features associated with desmoplakin mutations reported in medical literature illustrates the complexity of this group of disorders and their genotype–phenotype correlations, which cannot be easily predicted. Our reported case is a paradigmatic example of diagnostic difficulties often encountered when facing concomitant dermatological and oral conditions in the same patient, emphasizing the importance of recognizing oral, dental and skin signs to be a potential risk factor for hidden cardiac diseases.
DP16 Trichilemmocysticus naevus: a rare birthmark treated successfully with erbium ablative laser
Authors: Hannah Bennett, Rachel Urwin, Will Merchant
Journal: British Journal of Dermatology (2023)

Abstract We report a rare case of a 58-year-old woman with a naevus trichilemmocysticus. The patient presented to a tertiary dermatology centre with longstanding skin changes to her trunk. The changes had been apparent since childhood and became more prominent in her teens. Examination showed a linear Blaschkoid distribution of subtle hyperpigmentation and warty follicular prominence to the left submammary region, extending to the left upper back, where comedones and cystic papules were also noted. Histopathology confirmed the presence of cysts containing keratin, lined by trichilemmal-type squamous epithelium, representing trichilemmal cysts. The overlying epidermis appeared normal. Given the Blaschkoid distribution and the presence since childhood, it was thought that this most likely represented a naevus trichilemmocysticus. Tantcheva-Poor et al. described and named this as a rare type of organoid naevus-type lesion in 2007 (Tantcheva-Poor I, Reinhold K, Krieg T, Happle R. Trichilemmal cyst nevus: a new complex organoid epidermal nevus. J Am Acad Dermatol 2007; 57:S72–7). Only seven cases have been identified and reported in the literature. These have been characterized by multiple follicular filiform hyperkeratoses and trichilemmal cysts in a Blaschkoid distribution. Most cases described involve extensive areas of the skin and present with disfiguring lesions. Histology reports confirm epidermal acanthosis with deep invaginations filled with massive orthokeratosis, parakeratotic columns and an absent granular layer (isthmic or trichilemmal differentiation) with keratosis in sebaceous ducts and acrosyringia. Our patient is currently undergoing successful treatment with erbium laser under local anaesthesia, in order to improve the texture and appearance of the birthmark. This has been achieved by ablation to the warty areas to the level of upper papillary dermis, with focal deeper ablation to the skin overlying each cyst, followed by the use of a meibomian cyst curette for enucleation.
P02 Galli Galli disease: a rare variant of the genodermatosis Dowling–Degos disease
Authors: Paula Beatty, Mairin Mc Menamin, Bairbre Wynne
Journal: British Journal of Dermatology (2023)

Abstract A 35-year-old woman presented with a 4-year history of a persistent pruritic rash affecting her upper and lower limbs, concerning to the patient for cosmetic reasons. She denied any precipitating factors and reported no improvement with the use of topical clobetasol propionate. Notably, her mother had a similar rash, which had also developed in her 30s and continued to progress over time. Physical examination revealed a bilateral symmetrical papular eruption with superficial scale affecting extensor surfaces of her upper and lower limbs. The patient’s mother was also reviewed and had similar clinical findings, although a more generalized distribution was noted. Skin biopsy from the right thigh of the daughter showed acantholysis in the stratum spinosum with dyskeratotic cells. Biopsy from the left thigh of the patient’s mother showed elongation of rete ridges with foci of increased basal pigmentation and intraepidermal acantholysis. The presence of acantholysis and elongation of rete ridges with basal pigmentation histologically confirmed the diagnosis of the Galli–Galli variant of Dowling–Degos disease (DDD). The genetic basis for DDD involves a heterozygous loss of expression mutation affecting KRT5. Other implicated mutations include POGLUT1, POFUT1 and PSENEN, which are important in melanosome transfer, and the differentiation of melanocytes and keratinocytes. Galli–Galli disease remains a therapeutic challenge. Reported treatments trialled include topical retinoids, oral corticosteroids, and narrowband ultraviolet, although the outcomes have been disappointing. Successful treatment with erbium : yttrium aluminium garnet laser has been reported. Owing to the progressive nature of this condition, patient counselling regarding treatment expectations is important.
PD03 Afamelanotide reduces the ultraviolet radiation erythemal response soon after application in healthy volunteers with skin phototypes II–III
Authors: Liezel Griffin, Jessica Nucci, Pilar Bilbao, Lesley Rhodes, Mark Farrar
Journal: British Journal of Dermatology (2023)

Abstract Afamelanotide is a potent α-melanocyte stimulating hormone analogue that binds to the melanocortin 1 receptor and, over time, promotes tanning, conferring systemic photoprotection. Afamelanotide also has antioxidant properties and may promote repair of ultraviolet (UV) radiation (UVR)-induced DNA damage. The objectives of this study were to examine the short-term impact of afamelanotide on DNA damage repair mechanisms, UVR erythema and melanogenic responses in healthy human skin following exposure to UVR. Healthy men and women (n = 10) volunteers aged 27–43 years (median 34) of skin phototypes II–III were recruited. Reflectance spectrophotometry was performed on six body sites (photoexposed and photoprotected) to assess skin pigmentation, and then a geometric series of erythemally weighted doses (7–80 mJ cm−2) of broadband UVB (∼60% UVB, 40% UVA; Philips TL12) was applied to unexposed upper buttock skin. After 24 h, the minimal erythema dose (MED) was assessed and erythema intensity (CIE a*) was measured at each dose site. A subcutaneous implant of afamelanotide 16 mg was administered; 5 days later, the same UVR dose series was applied to unexposed contralateral upper buttock skin. After 24 h, the MED was assessed and repeat skin reflectance measurements were performed. The overall UVR–erythema dose response (area under curve) showed a significant decrease post-afamelanotide (mean 3.5 vs. 2.7; P = 0.018). There was an apparent increase in the median MED post-afamelanotide (24.5 vs. 29.9 mJ cm−2; not statistically significant). Reflectance measurements showed skin lightness (CIE L*) significantly decreased at only one site (central forehead, from 63.0 to 61.0; P = 0.015), while determination of melanin density by reflectance at 420 and 400 nm showed a statistically significant increase in density at all sites except the right abdomen, with a mean overall increase from 2.5% to 2.9% (P = 0.001). Our results indicate that afamelanotide reduces the overall UVR–erythema dose response in healthy human skin shortly after administration, with a small increase in melanogenesis, suggesting other nonmelanogenic properties of this agent contribute to the erythema protection. Further investigation will examine whether enhanced repair of UVR-induced DNA damage plays a role. Funding sources: research sponsored by CLINUVEL (UK) Ltd.
P64 Efficacy of baricitinib in patients with different degrees of severe alopecia areata: 52-week results from BRAVE-AA1 and BRAVE-AA2
Authors: Paul Farrant, Alexander Egeberg, Taisuke Ito, Beatrice Gittens, Chiara Chiasserini, Guanglei Yu, Frederick Durand, Yu-Huei Huang
Journal: British Journal of Dermatology (2023)

Abstract Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, demonstrated efficacy in adults with severe alopecia areata (AA) over 36 weeks in two phase III, randomized, double-blind, placebo-controlled trials, BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259). Using integrated data from the long-term extension periods of both trials, we report treatment response to baricitinib by the AA severity subgroup based on the Severity of Alopecia Tool (SALT) score over 52 weeks. Patients randomized to baricitinib at baseline (n = 855) retained their treatment allocation (2 mg/4 mg) through to week 52 in both trials and were included in week 52 analyses; placebo nonresponders were rescued at week 36. Severity of AA at baseline was defined as severe (SALT score 50–94) or very severe (SALT score 95–100). Key inclusion criteria were SALT score ≥ 50, current AA episode lasting &amp;gt; 6 months to &amp;lt; 8 years without spontaneous improvement within 6 months prior to screening, and no previous inadequate response to oral JAK inhibitors. Efficacy endpoints included the proportion of patients achieving a SALT score ≤ 20 and the proportion of patients achieving Clinician-Reported Outcome (ClinRO) Measure for Eyebrow/Eyelash Hair Loss™ 0,1 (no, minimal gaps) with ≥ 2-point improvement from baseline among patients with baseline scores 2,3 (significant gaps, no notable eyebrows/eyelashes). Analyses were presented descriptively for each subgroup up to week 52. Nonresponder imputation was used for missing data. Data collected after permanent study drug discontinuation or at remote visits due to the COVID-19 pandemic were excluded. In total, 1200 patients were enrolled (BRAVE-AA1, n = 654; BRAVE-AA2, n = 546). At baseline, the overall mean (SD) age was 37.5 (12.9) years; 60.7% were female and 46.8% and 53.2% of patients had severe and very severe AA, respectively. At week 52, a SALT score ≤ 20 was achieved by 36.1% and 51.2% of patients on baricitinib 2 mg and baricitinib 4 mg, respectively, with severe AA and 12.4% and 27.7% of patients on baricitinib 2 mg and baricitinib 4 mg, respectively, with very severe AA. Eyebrow/Eyelash Hair Loss™ scores 0,1 with ≥ 2-point improvement from baseline at week 52 were achieved by 19.4% and 26.0% (baricitinib 2 mg) and 37.5% and 38.5% (baricitinib 4 mg) of patients with severe AA and 24.3% and 25.3% (baricitinib 2 mg) and 47.6% and 48.1% (baricitinib 4 mg) of patients with very severe AA. Following 52 weeks of treatment with both baricitinib doses, clinical responses of SALT score ≤ 20 were observed both in patients with severe and very severe AA. Proportions of patients achieving full coverage or minimal gaps in eyebrows and eyelashes were similar at week 52, regardless of scalp hair-loss severity. Funding sources: Eli Lilly and Company.
BT03 (P63) Effectiveness of an image-analysing artificial intelligence-based digital health technology to diagnose nonmelanoma skin cancer and benign skin lesions
Authors: Helen Marsden, Ioulios Palamaras, Polychronis Kemos, Jack Greenhalgh
Journal: British Journal of Dermatology (2023)

Abstract Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are common types of nonmelanoma skin cancer (NMSC). The DERM-003 study was a prospective multicentre single-arm masked study that aimed to demonstrate the effectiveness of an artificial intelligence-based digital health technology (AI-DHT) to identify SCC, BCC and premalignant conditions in dermoscopic images of suspicious skin lesions. Patients with at least one suspicious skin lesion that was suitable for photography were eligible. Each lesion was photographed with three smartphone cameras (iPhone 6S, iPhone 11 and Samsung 10) with a dermoscopic lens attached. Each image was assessed by the AI-DHT. A clinical diagnosis was made by the dermatologist, and histopathology results were obtained for biopsied lesions. The AI-DHT output was compared with the histopathology diagnosis, and the area under the receiver operating characteristic curve (AUROC) was calculated. Secondary endpoints included other diagnostic measures and assessment of premalignant lesions. Altogether, 572 patients (49.5% women, mean age 68.5 years, 96.9% Fitzpatrick skin types I–III) were recruited from four UK National Health Service trusts, providing images of 611 suspicious lesions. There were no exclusion criteria relating to skin type. In total, 592 lesions had images from all three cameras available; only one lesion had no images available. Altogether, 395 lesions had a histopathology result. Forty-seven biopsied lesions were diagnosed as SCC and 184 as BCC. The AUROCs for images taken by the iPhone 6S was 0.88 [95% confidence interval (CI) 0.83–0.93] for SCC and 0.87 (95% CI 0.84–0.91) for BCC. For the Samsung 10, the AUROCs were 0.85 (95% CI 0.79–0.90) and 0.87 (95% CI 0.83–0.90), and for the iPhone 11, they were 0.88 (95% CI 0.84–0.93) and 0.89 (95% CI 0.86–0.92) for SCC and BCC, respectively. Using images taken on the iPhone 6S of biopsied only lesions, the sensitivity in detecting SCC and BCC was 98% (95% CI 88–100) and 94% (95% CI 90–97), respectively; the specificity was 38% (95% CI 33–44) and 28% (95% CI 21–35), respectively; the positive predictive value was 17% (95% CI 16–19) and 59% (95% CI 56–61), respectively; and the NPV was 99% (95% CI 95–100) and 81% (95% CI 70–89), respectively. All 12 lesions diagnosed as Bowen disease were classified correctly by the AI-DHT. Of the 61 lesions diagnosed as actinic keratosis, 52 were correctly classified of the 22 lesions diagnosed as dysplastic, and 18 were correctly classified by the AI-DHT. All 16 lesions diagnosed as melanoma were classified as such by the AI-DHT. The AI-DHT has the potential to support the diagnosis of NMSC and premalignant lesions.
P106 Hidradenitis suppurativa is associated with lower socioeconomic status using the MacArthur scale of subjective social status
Authors: Niamh Kearney, Barry McGrath, Collette McCourt, Rosalind Hughes, Donal O’Kane, Brian Kirby
Journal: British Journal of Dermatology (2023)

Abstract Hidradenitis suppurativa (HS) is associated with lower socioeconomic status (SES). Previous studies in Europe, Australia and the USA identified that patients with HS are more likely to be unemployed and have lower mean incomes than the background population. Low SES is inextricably linked with poor health outcomes. The MacArthur scale of subjective social status is a simple ladder from 1 to 10 that describes perceived SES and is an even better predictor of health outcomes than objective measures of SES. Our aim was to evaluate SES in HS using the MacArthur scale and compare it with healthy controls. Patient recruitment took place in two dermatology clinics where all patients with HS were invited to participate in addition to an anonymous online survey distributed by HS patient-led organizations. Healthy control patients were recruited from a rapid-access lesion clinic. Statistical analysis was completed using Jamovi (version 2.0). Student’s t-test was used to compare means and Spearman’s test for correlation. We recruited 131 patients with HS with a mean age of 37.6 years and 82 healthy controls with a mean age of 48.7 years. Patients with HS were predominantly female (89.3%) as were healthy controls (62.2%). The mean (SD) MacArthur scale in the HS group was 4.85 (2.19) (range 1–10). It was higher in healthy control patients at 6.44 (1.36) (range 3–10; P &amp;lt; 0.001). In the HS cohort, the mean MacArthur scale was higher in employed patients (5.49 vs. 3.59; P &amp;lt; 0.001) and in patients who completed any education following school (5.19 vs. 4.12; P = 0.009). The MacArthur scale weakly but statistically significantly correlated with age (r = 0.158, P = 0.022) and was higher in male patients (6.14 vs. 5.27; P = 0.013). Owing to the influence of age and sex on the MacArthur scale, a group of 37 patients with HS with age- and sex-matched healthy controls was analysed. In this matched group, the mean MacArthur scale was lower in patients with HS (5.22 vs. 6.36; P = 0.018). This is the first study to assess SES in HS using the MacArthur scale of the subjective social status. Patients with HS had a significantly lower SES than healthy controls. The MacArthur scale accounted for both employment and education in the HS cohort. The ladder is easy to use and provides more information with regard to health outcomes than objective SES alone. Its use should be considered in HS research, particularly studies evaluating treatment response, disease and comorbidity outcomes.